Scratching

Abstract: The standard rodent model of itch uses scratching with the hind limb as a behavioral response to pruritic stimuli applied to the nape of the neck. The assumption is that scratching is an indicator of the sensation of itch. But because only one type of site-directed behavior is available, one cannot be certain that scratching is not a response to nociceptive or other qualities of sensations in addition to, or instead of, itch. To extend the model, we administered chemical stimuli to the cheek of the mouse and counted scratching with the hind limb as an indicator of itch and wiping with the forelimb as an indicator of pain. An intradermal injection of histamine and capsaicin, known to evoke predominantly itch and pain, respectively, in humans, each elicited hind limb scratching behavior when injected into the nape of the neck of the mouse. In contrast, when the same chemicals were injected into the cheek of the mouse, there were two site-directed behaviors: histamine again elicited scratching with the hind limb, but capsaicin evoked wiping with the forelimb. We conclude that the “cheek model of itch” in the mouse provides a behavioral differentiation of chemicals that elicit predominantly itch in humans from those that evoke nociceptive sensations. That is, the model provides a behavioral differentiation between itch and pain in the mouse.

Abstract: Our experiments were conducted to determine whether substance P (SP) would elicit an itch sensation mediated by mast cells in mice. An intradermal injection of SP (10-135 microgram site-1) into the rostral back of the ICR mouse dose-dependently produced scratching of the injected site. The SP- (135 microgram site-1 = 100 nmol site-1) induced scratching was inhibited by capsaicin (repeated administration) and naloxone; features being similar to itch in humans. SP elicited scratching in mast cell-deficient (WBB6F1 W/Wv) mice as well as control (+/+) mice. Pretreatment with compound 48/80 produced similar degrees of inhibition of SP-induced scratching in mast cell-deficient mice as well as control +/+ and ICR mice. Intradermal injections of the NK1 receptor agonist GR73632 produced dose-dependent scratching, while the NK2 agonist GR64349 and the NK3 agonist senktide were without effects. SP-induced scratching was inhibited by the NK1 receptor antagonists spantide and L-668,169, but not by the NK2 antagonist L-659,877. The results suggest that scratching of the mouse induced by an i.d. injection of SP is itch-associated response. The SP action may be mediated at least partly by cutaneous NK1 receptors, and mast cells may not be key factors in SP-induced itching.

Abstract: Pruritus is an important symptom in atopic dermatitis (AD), but the major pruritogen have not been identified. NC/Nga mice, spontaneously develop an eczematous AD-like skin lesion when kept under conventional conditions, but not under specific pathogen-free (SPF) conditions, have been thought to be an animal model for AD. In this study, to determine whether newly identified cytokine, IL-31, may be involved in pruritus of AD, we examined the IL-31 expression in spontaneous dermatitis model which showed itch-associated long-lasting (over 1.5 s duration) scratching behavior and compared with that of hapten-induced contact dermatitis model without itch-associated long-lasting scratching behavior, using NC/Nga mice. In NC/Nga mice cohabited with NC/Nga mice which developed severe dermatitis for 2 weeks (conventional NC/Nga mice), the numbers of long-lasting scratching counts were significantly increased. Yet in 2,4,6-trinitrochlorobenzene (TNCB)-sensitized and challenged mice (TNCB-applied NC/Nga mice), no significant increase in long-lasting scratching counts was observed. In conventional NC/Nga mice with long-lasting scratching behavior, expression of IL-31 mRNA was increased, while in TNCB-applied NC/Nga mice without long-lasting scratching behavior, the expression of IL-31 mRNA were unchanged. There was a good correlation between the scratching counts and expression of IL-31 mRNA in conventional NC/Nga mice, but not so in TNCB-applied NC/Nga mice. These results suggest that IL-31 causes the itch-associated scratching behavior in conventional NC/Nga mice, an experimental animal model for AD.